Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-β in bronchial epithelial cells from donors with asthma
Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-β in bronchial epithelial cells from donors with asthma
复制标题
DOI：
10.1136/thx.2009.125930
复制
发表时间：
2010-07-01
期刊：
影响因子：
10
通讯作者：
Davies, Donna E.
中科院分区：
文献类型：
--
作者：
Uller, Lena;Leino, Marina;Davies, Donna E.
背景胸腺基质淋巴细胞生成素（TSLP）是一种上皮细胞源性细胞因子，可强烈激活树突状细胞，并可引发过敏性炎症。由于暴露于鼻病毒或双链（ds）RNA目的哮喘患者支气管上皮细胞（BEC）对鼻病毒感染的干扰素（IFN）应答不足，因此TSLP可能是BEC抗病毒应答和2型适应性免疫应答的重要环节。进行了一项研究以检验其抗病毒应答显示偏向TSLP产生的假设。方法原代BEC从哮喘受试者和健康志愿者中生长。RT-qPCR和ELISA分别检测BECs中IL-8、IFN β和TSLP mRNA和蛋白的表达。然而，哮喘患者的BEC表达较少的IFN β和更多的TSLP mRNA和蛋白质对dsRNA的反应比非哮喘患者的BEC（中位数（IQR）57（38-82）pg/ml vs 106（57-214）pg/ml）（IFN β）（p
Background Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells and can initiate allergic inflammation. Since exposure to rhinovirus or double-stranded (ds) RNA (a surrogate of viral infection) induces TSLP expression in bronchial epithelial cells (BECs), this cytokine may link innate antiviral responses and the type 2 adaptive immune response.Objective As BECs from donors with asthma have a deficient interferon (IFN) response to rhinovirus infection, a study was undertaken to test the hypothesis that their antiviral response shows a bias towards TSLP production.Methods Primary BECs were grown from subjects with asthma and healthy volunteers. After exposure to dsRNA, interleukin (IL)-8, IFN beta and TSLP mRNA and protein expression were measured by RT-qPCR and ELISA, respectively.Results dsRNA dose-dependently increased IL-8 expression in BECs with no significant difference between the groups. However, BECs from subjects with asthma expressed less IFN beta and more TSLP mRNA and protein in response to dsRNA than BECs from those without asthma (median (IQR) 57 (38-82) pg/ml vs 106 (57-214) pg/ml for IFN beta (p